Sheng X Rebecca, Posenau Trevor, Gumulak-Smith Juliann J, Matunis Erika, Van Doren Mark, Wawersik Matthew
Department of Cell Biology, 725 N. Wolfe Street, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Dev Biol. 2009 Oct 15;334(2):335-44. doi: 10.1016/j.ydbio.2009.07.031. Epub 2009 Jul 28.
Germline stem cells (GSCs) in Drosophila are descendants of primordial germ cells (PGCs) specified during embryogenesis. The precise timing of GSC establishment in the testis has not been determined, nor is it known whether mechanisms that control GSC maintenance in the adult are involved in GSC establishment. Here, we determine that PGCs in the developing male gonad first become GSCs at the embryo to larval transition. This coincides with formation of the embryonic hub; the critical signaling center that regulates adult GSC behavior within the stem cell microenvironment (niche). We find that the Jak-STAT signaling pathway is activated in a subset of PGCs that associate with the newly-formed embryonic hub. These PGCs express GSC markers and function like GSCs, while PGCs that do not associate with the hub begin to differentiate. In the absence of Jak-STAT activation, PGCs adjacent to the hub fail to exhibit the characteristics of GSCs, while ectopic activation of the Jak-STAT pathway prevents differentiation. These findings show that stem cell formation is closely linked to development of the stem cell niche, and suggest that Jak-STAT signaling is required for initial establishment of the GSC population in developing testes.
果蝇中的生殖系干细胞(GSCs)是胚胎发育过程中特化的原始生殖细胞(PGCs)的后代。睾丸中GSC建立的确切时间尚未确定,控制成年期GSC维持的机制是否参与GSC建立也不清楚。在这里,我们确定发育中的雄性性腺中的PGCs在胚胎向幼虫转变时首次成为GSCs。这与胚胎枢纽的形成同时发生;胚胎枢纽是调节干细胞微环境(生态位)内成年GSC行为的关键信号中心。我们发现Jak-STAT信号通路在与新形成的胚胎枢纽相关的一部分PGCs中被激活。这些PGCs表达GSC标志物并具有GSCs的功能,而不与枢纽相关的PGCs则开始分化。在没有Jak-STAT激活的情况下,与枢纽相邻的PGCs无法表现出GSCs的特征,而Jak-STAT通路的异位激活则可防止分化。这些发现表明干细胞的形成与干细胞生态位的发育密切相关,并表明Jak-STAT信号是发育中的睾丸中GSC群体初始建立所必需的。